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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01950273




Registration number
NCT01950273
Ethics application status
Date submitted
23/09/2013
Date registered
25/09/2013
Date last updated
5/09/2018

Titles & IDs
Public title
Pharmacokinetics and Pharmacodynamics of BI 695500 vs. Rituximab as First Line-treatment in Patients With Low Tumor Burden Follicular Lymphoma
Scientific title
A Randomized, Double-blind, Parallel-arm, Phase I Study to Evaluate the Pharmacokinetics and Pharmacodynamics of BI 695500 vs. Rituximab (MabThera) Induction Immunotherapy as a First-line Treatment in Patients With Low Tumor Burden Follicular Lymphoma
Secondary ID [1] 0 0
2013-001904-12
Secondary ID [2] 0 0
1301.5
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma, Follicular 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BI 695500
Treatment: Drugs - MabThera

Experimental: BI695500 - BI695500, once a week for 4 weeks (4 administrations in total)

Active Comparator: MabThera - MabThera, once a week for 4 weeks (4 administration in total)


Treatment: Drugs: BI 695500
BI695500, once a week for 4 weeks (4 administrations in total)

Treatment: Drugs: MabThera
MabThera, once a week for 4 weeks (4 administrations in total)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area Under the Concentration (AUC) Time Curve of BI 695500 and Rituximab (MabThera®) Over the First Dosing Interval (Pre-infusion on Day 1 to Pre-infusion on Day 8)
Timepoint [1] 0 0
Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion 1, and at 24, 48, 72, 96 and 168 hours from start of infusion 1.
Secondary outcome [1] 0 0
AUC of BI 695500 and Rituximab (MabThera®) Over the Fourth Dosing Interval (Pre-infusion on Day 22 to Day 29) (AUC Day 22-Day 29)
Timepoint [1] 0 0
Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion 4, and at 24, 48, 72, 96 and 168 hours from start of infusion 4.
Secondary outcome [2] 0 0
Maximum Measured Concentration of BI 695500 and Rituximab (MabThera®) in Plasma (Cmax) Following Dose 1
Timepoint [2] 0 0
Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion 1, and at 24, 48, 72, 96 and 168 hours from start of infusion 1.
Secondary outcome [3] 0 0
Maximum Measured Concentration of Rituximab (MabThera®) and BI 695500 in Plasma (Cmax) Following Dose 4
Timepoint [3] 0 0
Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion 4, and at 24, 48, 72, 96, 168, 336, 672, 1344, 2016 and 2880 hours from start of infusion 4.
Secondary outcome [4] 0 0
Area Under the Depletion-time Curve of the Cluster of Differentiation (CD)19+ B-cell Count (% Change From Baseline (CFB)) in Peripheral Blood From Pre-infusion on Day 1 Until Last Measurement on Day 8 (Pre-infusion)
Timepoint [4] 0 0
Blood samplings were done at pre-infusion and at end of infusion at 1, 2, and 4 hours from end of infusion, and at 24, 48, 72, 96 and 168 hours from start of infusion.
Secondary outcome [5] 0 0
Change From Baseline (%) of CD19+ B-cells in Peripheral Blood Measured After Seven Days on Day 8 (Day 8 Pre-infusion Time Point)
Timepoint [5] 0 0
Blood sampling was done at 168 hours from start of infusion.
Secondary outcome [6] 0 0
Overall Response Rate (ORR) (Complete Response (CR) Plus Partial Response (PR)) Evaluated Approximately One Month After Last Dose of BI 695500 or Rituximab (MabThera®)
Timepoint [6] 0 0
at Day 50.
Secondary outcome [7] 0 0
Percentage of Patients With Treatment Emergent Adverse Events (TEAEs) Selected for Comparability Assessment of BI 695500 and Rituximab (MabThera®)
Timepoint [7] 0 0
Adverse Events (AEs) that started or worsened on or after the first dose of study medication and prior to the last date of study medication + 4 months (120 days) inclusive.

Eligibility
Key inclusion criteria
Inclusion criteria:

- Must give written informed consent and be willing to follow this Clinical Trial
Protocol.

- Male or female patients, at least 18 years of age at Screening.

- Histologically-confirmed, stage II - IV Non-Hodgkin's lymphoma (CD20+ FL of Grades 1,
2, or 3a).

- Low tumor burden according to the Groupe d'Etudes des Lymphomes Folliculaires (GELF)
criteria - no nodal or extranodal involvement of more than 7 cm, no more than 3 nodal
sites with a diameter >3 cm, no B symptoms (i.e., fever >38°C, weight loss -
unexplained loss of >10 % body weight over the past 6 months, and sweats - the
presence of drenching night sweats), no significant splenomegaly, no significant
serious effusion, no complications such as organ compression, and less than 5x10^9/L
circulating tumor cells.

- Availability of archived tumor sample prior to screening.

- Patients not previously treated for their FL.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

- Have at least 1 measurable lesion as per the International Working Group (IWG)
criteria 2007 at Screening (lesion clearly measurable in at least 2 perpendicular
dimensions; see Appendix 10.1 for further details).

- Adequate hematological function (unless abnormalities are related to lymphoma
infiltration of the bone marrow) within 28 days prior to randomization, including:

- - hemoglobin =9.0 g/dL (=5.6 mmol/L).

- - absolute neutrophil count =1.5 × 10^9/L.

- - platelet count =100 × 10^9/L.

- Adequate renal and liver function:

- - serum creatinine <2.0 mg/dL (<176.8 micromol/L).

- - total bilirubin <2.0 mg/dL (<34 mcmol/L) except for patient with Gilbert's Syndrome
or Hemolysis. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 x
upper limit of normal (ULN) (<5 x ULN is acceptable if abnormalities are thought to be
related to hepatic infiltration by FL).

- For participants of reproductive potential (males and females), use of a medically
acceptable method of contraception during the trial, i.e., a combination of 2 forms of
effective contraception (defined as hormonal contraception, intrauterine device,
condom with spermicide, etc.). Females of childbearing potential (includes tubal
ligation) and males with female partners of childbearing potential must also agree to
use an acceptable method of contraception (see above) for 12 months following
completion or discontinuation from the trial medication.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Transformation to high-grade lymphoma (secondary to low-grade lymphoma).

- Presence or history of central nervous system lymphoma.

- Patients receiving current treatment with corticosteroids must not be receiving a dose
exceeding 20 mg/day prednisone or equivalent.

- Patients with prior or concomitant malignancies within 5 years prior to screening
except non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix,
adequately treated breast cancer in situ, localized prostate cancer stage T1c -
provided that the patient underwent curative treatment, and remains relapse free.

- Major surgery (excluding lymph node biopsy) within 28 days prior to randomization.

- Active, chronic or persistent infection that might worsen with immunosuppressive
treatment (e.g., Human Immunodeficiency Virus [HIV], Hepatitis C Virus [HCV], Herpes
Zoster); positive for HIV or tuberculosis at Screening.

- Patients with serological evidence of Hepatitis B virus (HBV) infection. Patients
seropositive because of HBV vaccine are eligible. HBV positive patients may
participate following consultation with a hepatitis expert regarding monitoring and
use of HBV antiviral therapy, and provided they agree to receive treatment as
indicated.

- Serious underlying medical conditions, which, per the investigator's discretion, could
impair the ability of the patient to participate in the trial (including but not
limited to ongoing active infection, severe immunosuppression, uncontrolled diabetes
mellitus, gastric ulcers, active autoimmune disease); patients who have significant
cardiac disease, including but not limited to congestive heart failure of Class III or
IV of the NYHA classification; uncontrolled angina or arrhythmia; any uncontrolled or
severe cardiovascular or cerebrovascular disease.

- Known hypersensitivity or allergy to murine products.

- History of a severe allergic reaction or anaphylactic reaction to a biological agent
or history of hypersensitivity to any component of the trial drug.

- Receipt of a live/attenuated vaccine within 12 weeks prior to the Screening Visit.

- Prior treatment with BI 695500 and/or rituximab.

- Patients who received any prior therapy using monoclonal antibodies will be excluded;
this does not apply to other biological drugs such as growth factors or
anticoagulants.

- Treatment within a clinical trial within 4 weeks prior to initiation of trial
treatment. Patients who have received treatment with a drug that has not received
regulatory approval for any indication within 4 weeks or a minimum of 5 half-lives,
whichever is longer, of the initial dose of trial medication.

- Any other co-existing medical or psychological condition(s) that will preclude
participation in the trial or compromise ability to give informed consent and/or
comply with study procedures.

- Pregnancy or breast feeding. For women of childbearing potential, a positive serum
pregnancy test at the Screening Visit.

- Patients who have significant cardiac disease, including but not limited to congestive
heart failure of Class III or IV of the New York Heart Association (NYHA)
classification; uncontrolled angina or arrhythmia; any uncontrolled or severe
cardiovascular or cerebrovascular disease; or uncontrolled hypertension.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/12/2015
Sample size
Target
Accrual to date
Final
95
Recruitment in Australia
Recruitment state(s)
Migration Dat
Recruitment hospital [1] 0 0
The Canberra Hospital - Canberra
Recruitment postcode(s) [1] 0 0
2605 - Canberra
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Wien
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Belgium
State/province [4] 0 0
Namur
Country [5] 0 0
Croatia
State/province [5] 0 0
Zagreb
Country [6] 0 0
Czechia
State/province [6] 0 0
Brno
Country [7] 0 0
Czechia
State/province [7] 0 0
Ostrava-Poruba
Country [8] 0 0
Czechia
State/province [8] 0 0
Praha 2
Country [9] 0 0
France
State/province [9] 0 0
Bordeaux cedex
Country [10] 0 0
France
State/province [10] 0 0
Brest
Country [11] 0 0
France
State/province [11] 0 0
La Roche sur Yon
Country [12] 0 0
France
State/province [12] 0 0
Pessac
Country [13] 0 0
France
State/province [13] 0 0
Poitiers
Country [14] 0 0
Germany
State/province [14] 0 0
Bad Nauheim
Country [15] 0 0
Germany
State/province [15] 0 0
Dresden
Country [16] 0 0
Germany
State/province [16] 0 0
Freiburg
Country [17] 0 0
Germany
State/province [17] 0 0
Hamburg
Country [18] 0 0
Germany
State/province [18] 0 0
Kassel
Country [19] 0 0
Greece
State/province [19] 0 0
Athens
Country [20] 0 0
Hungary
State/province [20] 0 0
Budapest
Country [21] 0 0
New Zealand
State/province [21] 0 0
Auckland
Country [22] 0 0
Poland
State/province [22] 0 0
Warszawa
Country [23] 0 0
Russian Federation
State/province [23] 0 0
Omsk
Country [24] 0 0
Russian Federation
State/province [24] 0 0
St. Petersburg
Country [25] 0 0
Spain
State/province [25] 0 0
Badalona
Country [26] 0 0
Spain
State/province [26] 0 0
Cádiz
Country [27] 0 0
Spain
State/province [27] 0 0
Madrid
Country [28] 0 0
Spain
State/province [28] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the study is to assess the pharmacokinetic (PK) similarity of
Boehringer Ingelheim (BI) 695500 vs. rituximab (MabThera®) in previously untreated patients
with low tumor burden follicular lymphoma (LTBFL).

The secondary objective of the study is to evaluate the pharmacodynamics (PD), safety, and
anti-tumor activity of BI 695500 vs. rituximab (MabThera®), as well as the presence of
anti-drug antibodies (ADAs).
Trial website
https://clinicaltrials.gov/ct2/show/NCT01950273
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01950273